High Blood Pressure in Children and Adolescents: Screening
November 10, 2020
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
By Gerald Gartlehner, MD, MPH; Emily B. Vander Schaaf, MD, MPH; Colin Orr, MD; Sara M. Kennedy, MPH; Rachel Clark, BA; Meera Viswanathan, PhD.
The information in this article is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This article is intended as a reference and not as a substitute for clinical judgment.
This article may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.
This article was published online in JAMA on November 10, 2020 (JAMA. 2020;324(18):1884-1895. doi:10.1001/jama.2020.11).
Importance: Childhood hypertension can result in adverse outcomes during adulthood; identifying and treating primary and secondary childhood hypertension may reduce such risks.
Objective: To update the evidence on screening and treatment of hypertension in childhood and adolescence for the US Preventive Services Task Force.
Data Sources: PubMed, Cochrane Library, International Pharmaceutical Abstracts, EMBASE, and trial registries through September 3, 2019; bibliographies from retrieved articles, experts, and surveillance of the literature through October 6, 2020.
Study Selection: Fair- or good-quality English-language studies evaluating diagnostic accuracy of blood pressure screening; cohort studies assessing the association of hypertension in childhood and adolescence with blood pressure or other intermediate outcomes in adulthood; randomized clinical trials (RCTs) or meta-analyses of pharmacological and lifestyle interventions.
Data Extraction and Synthesis: Two reviewers independently assessed titles/abstracts and full-text articles, extracted data, and assessed study quality; the evidence was synthesized qualitatively.
Main Outcomes and Measures: Sensitivity, specificity, and measures of association between childhood and adulthood blood pressure; reduction of childhood blood pressure; adverse effects of treatments.
Results: Forty-two studies from 43 publications were included (N>12,400). No studies evaluated the benefits or harms of screening and the effect of treating childhood hypertension on outcomes in adulthood. One study reported a sensitivity of 0.82 and a specificity of 0.70 for 2 office-based blood pressure measurements. Twenty observational studies suggested a significant association between childhood hypertension and abnormal blood pressure in adulthood (odds ratios, 1.1-4.5; risk ratios, 1.45-3.60; hazard ratios, 2.8-3.2). Thirteen placebo-controlled RCTs and 1 meta-analysis assessed reductions in systolic (SBP) and diastolic blood pressure from pharmacological treatments. Pooled reductions of SBP were −4.38 mm Hg (95% CI, −7.27 to −2.16) for angiotensin-converting enzyme inhibitors and −3.07 mm Hg (95% CI, −4.99 to −1.44) for angiotensin receptor blockers. Candesartan reduced SBP by −6.56 mm Hg (P < .001; n = 240). β-Blockers, calcium channel blockers, and mineralocorticoid receptor antagonists did not achieve significant reductions over 2 to 4 weeks. SBP was significantly reduced by exercise over 8 months (−4.9 mm Hg , P ≤ .05; n = 69), by dietary approaches to stop hypertension over 3 months (−2.2 mm Hg , P < .01; n = 57), and by a combination of drug treatment and lifestyle interventions over 6 months (−7.6 mm Hg ; P < .001; n = 95). Low-salt diet did not achieve reductions of blood pressure.
Conclusions and Relevance: Observational studies indicate an association between hypertension in childhood and hypertension in adulthood. However, the evidence is inconclusive whether the diagnostic accuracy of blood pressure measurements is adequate for screening asymptomatic children and adolescents in primary care.
The American Academy of Pediatrics defines hypertension in children aged 1 to 13 years as auscultatory systolic or diastolic blood pressure measurements that, according to 3 separate measurements, are either at or above 130/80 mm Hg or equal to or above the 95th percentile for children of the same sex and age or height (Table 1).1 In adolescents 13 years or older, thresholds mirror guidelines for adults.1 Primary hypertension does not have an identifiable cause; secondary hypertension is most commonly caused by renal or renovascular disease, endocrine disorders, cardiac abnormalities, or genetic disorders.2 In asymptomatic children, hypertension may be the only sign of such an underlying condition. The overall prevalence of hypertension in children and adolescents in studies conducted between 1999 and 2014 in the US ranged between 1.6% and 3.6%.3-6
Children with primary hypertension are at higher risk of developing adverse intermediate cardiovascular outcomes, such as increased left ventricular mass, carotid intima-media thickness, and increased pulse wave velocity.7 The association between such intermediate outcomes in childhood and health outcomes in adulthood, however, is unclear. Screening for hypertension in childhood and adolescence may lead to earlier treatment, therefore reducing the risk of adult hypertension and cardiovascular complications.
This review was conducted to inform the US Preventive Services Task Force (USPSTF) in preparing an updated recommendation statement. Based on an updated systematic review,8 in 2013 the USPSTF concluded that the evidence was insufficient to assess the balance of benefits and harms of screening for primary hypertension in asymptomatic children and adolescents to prevent subsequent cardiovascular disease in childhood and adulthood (I statement).9
Scope of the Review
Compared with the previous review,8 the population of interest was extended to children and adolescents with secondary hypertension, excluded pharmacological dose-ranging studies without a placebo group, and excluded results on harms from placebo-controlled withdrawal phases of trials.
Data Sources and Searches
PubMed, the Cochrane Library, International Pharmaceutical Abstracts, and EMBASE were searched for English-language articles published from June 1, 2012, through September 3, 2019. Because the previous review for the USPSTF did not include secondary hypertension, PubMed was searched from inception through September 3, 2019, and studies that the previous report excluded for “ineligible population” were rescreened. ClinicalTrials.gov, Cochrane Clinical Trials Registry, the World Health Organization International Clinical Trials Registry Platform, and Health Services Research Projects in Process were also searched. To supplement electronic searches, reference lists of pertinent articles and studies suggested by reviewers were searched. Ongoing surveillance was conducted through article alerts and targeted searches of journals to identify major studies published in the interim that may affect the conclusions or understanding of the evidence and the related USPSTF recommendation. The last surveillance was conducted on October 6, 2020.
Two investigators independently reviewed titles, abstracts, and full-text articles using prespecified inclusion criteria for each KQ; disagreements about inclusion were resolved by discussion or by a third reviewer. Briefly, eligible populations were asymptomatic children and adolescents for KQs 1 through 3 and participants with elevated blood pressure or hypertension for KQs 4 through 8. For KQ1 and KQ3, any study that compared screening with no screening was eligible for inclusion. For KQ2, studies reporting diagnostic test accuracy of blood pressure measurements that used a confirmed clinical diagnosis (ie, after diagnostic workup) of abnormal blood pressure as the reference test were included. For KQ4, eligible studies were longitudinal cohort studies that assessed the association of abnormal blood pressure during childhood and adult hypertension or other intermediate outcomes during adulthood. For KQs 5 through 8 on the effectiveness and harms of treatments, randomized clinical trials (RCTs) and large, controlled, observational studies (sample size >1000) were included; for KQ8 on harms, uncontrolled before-after studies were also accepted. For effectiveness, hypertension-related health outcomes (eg, cardiovascular events, end-stage kidney disease, or mortality) or intermediate outcomes (eg, blood pressure, left ventricular hypertrophy, or microalbuminuria) were of interest. For harms, labeling, anxiety, school absenteeism, and any treatment-related harms were included.
English-language studies that met all study selection criteria and that were of fair or good methodological quality were included. Studies included in the prior 2013 review were reassessed against the study selection and methodological quality criteria for this update.
Data Extraction and Quality Assessment
For each included study, 1 reviewer abstracted relevant study characteristics (ie, population, intervention, comparator) and data for eligible outcomes into a structured form. A second reviewer checked all data for completeness and accuracy. In cases of ambiguous or missing data, study authors were contacted. Two senior reviewers independently assessed each study’s methodological quality using predefined criteria established by the USPSTF.12 Disagreements in study quality ratings were resolved through discussion or with an independent assessment from a third senior investigator. Studies reporting multiple outcomes may have been assigned different quality ratings for different outcomes.
Data Synthesis and Analysis
Study characteristics and results of included studies were summarized in tabular or narrative format. Findings for all KQs were synthesized qualitatively. The strength of evidence was assessed based on the Agency for Healthcare Research and Quality Methods Guide for Effectiveness and Comparative Effectiveness Reviews, which specifies the assessment of study limitations, directness, consistency, precision, and reporting bias for each intervention comparison and major outcome of interest.13 Two senior reviewers independently developed initial strength-of-evidence assessments for each relevant outcome and comparison across the KQs; disagreements were resolved through discussion and the independent assessment of a third senior reviewer.
Forty-two studies (N>12,400) from 43 publications were included (Figure 2). One study was conducted among children 11 years or younger,14 2 studies enrolled adolescents between athe ages of 12 and 18 years,15,16 and the remaining studies included mixed populations of children and adolescents or did not report the age range at baseline.17,18 Because of slightly revised inclusion criteria, 4 RCTs from the previous report were excluded.19-22 The update included 1 study of test accuracy (KQ2),23 20 studies evaluated the association between abnormal blood pressure in childhood and abnormal blood pressure or other intermediate outcomes in adulthood (KQ4),17,18,24-41 20 RCTs14-16,42-58 and a meta-analysis59 assessed the effectiveness of pharmacological and nonpharmacological interventions (KQ5), and 7 RCTs provided data on harms (KQ8).42-47,55
Benefits of Screening
Key Question 1. Does screening for high blood pressure (ie, persistently elevated blood pressure or hypertension) in children and adolescents delay the onset of or reduce adverse health outcomes related to high blood pressure?
No studies were identified.
Accuracy of Screening
Key Question 2. What is the diagnostic accuracy of screening tests for high blood pressure in children and adolescents?
One fair-quality diagnostic test accuracy study (n = 247) assessed the sensitivity of 2 office-based blood pressure measurements, 1 to 2 weeks apart.23 Study characteristics are described in eTable 1 in the Supplement, and study methodological quality is presented in eTable 2 in the Supplement. The study enrolled healthy volunteers or patients referred for abnormal blood pressure who were 11 to 19 years old. Abnormal blood pressure for office-based measurements was defined according to the previous American Academy of Pediatrics recommendation.60 The reference standard was 26-hour ambulatory blood pressure monitoring (ABPM) at 20-minute intervals. Using systolic blood pressure (SBP) at the 90th percentile as a threshold, the sensitivity of 2 office-based blood pressure measurements was 0.82 (95% CI not reported) with a specificity of 0.70 (95% CI not reported) compared with ABPM.
Harms of Screening
Key Question 3. What are the adverse effects, such as labeling and anxiety, of screening for high blood pressure in children and adolescents?
No studies were identified.
Association of Childhood and Adult Hypertension
Key Question 4. What is the association between high blood pressure in children and adolescents and high blood pressure and other intermediate outcomes in adults?
Association Between Childhood and Adulthood Abnormal Blood Pressure
Twenty publications reported on the association between abnormal blood pressure in childhood and abnormal blood pressure or other intermediate outcomes in adulthood.17,18,24-41 Two studies did not report the age range of study participants at baseline;17,18 all other studies included mixed populations of children (mostly 3 to 11 years) and adolescents (12 to 18 years) at baseline. These studies drew from 9 databases (4 based in the US [1 unnamed cohort of school children in Boston, Massachusetts,24 the Fels Longitudinal Study,25,26 Bogalusa Heart Study,27-31,40 and Muscatine Study17,18], 2 based in Australia [Childhood Determinants of Adult Health study,39 Insulin study61], 1 based in Eastern Europe [Kaunas study62], 1 based in Finland [Young Finns32-37], and 1 based in New Zealand [the Dunedin Multidisciplinary Health and Development Study38]) that followed up cohorts of children into adulthood. The mean duration of follow-up ranged from 10 to 33 years. The risk of bias of these studies was not rated because risk-of-bias tools are designed to identify potential biases in causal inference rather than validity of associations.
Studies used various definitions of childhood and adulthood abnormal blood pressure (Table 2). Despite varying definitions, studies were generally consistent in demonstrating an association between abnormal blood pressure in childhood and abnormal blood pressure in adulthood.
The only study40 that used current definitions applied the 2017 American Academy of Pediatrics guidelines1 to categorize childhood blood pressure and the American Heart Association standards63 for adulthood blood pressure. It used data from the Bogalusa Heart Study,40 which followed up 3940 children over 25 years, on average. Children with elevated blood pressure had an increased risk (adjusted risk ratio [RR], 1.45 [95% CI, 1.30 to 1.61]) for developing hypertension as adults.
Nine studies relying on prior definitions of abnormal childhood or adulthood blood pressure also consistently found results for associations between abnormal blood pressure in childhood and abnormal blood pressure in adulthood, regardless of the definition of hypertension and methods of measurement (Table 2).31,33-40 Likewise, studies with nonstandard definitions of abnormal blood pressure (usually thresholds based on percentiles within the study cohort) reported associations between abnormal childhood and adulthood blood pressure (Table 2).17,18,24-27,30 Studies reported different measures of association such as odds ratios (ranging from 1.1 [95% CI, 0.5 to 2.4] to 4.5 [95% CI, 1.1 to 17.7]), RRs (ranging from 1.45 [95% CI, 1.30 to 1.61] to 3.60 [95% CI, 1.38 to 9.40]), and hazard ratios (ranging from 2.8 [95% CI, 2.0 to 3.9] to 3.2 [95% CI, 2.1 to 5.0]).
Association Between Abnormal Childhood Blood Pressure and Other Intermediate Outcomes in Adulthood
Seven studies28,29,31,32,36,40,41 examined the relationship between abnormal childhood or adolescent (age range, 3-18 years) blood pressure and intermediate outcomes (other than blood pressure) in adults. Only 1 study used current definitions of hypertension in children.40 Regardless of definitions used, 6 studies generally reported statistically significant associations between abnormal childhood blood pressure and carotid intima-media thickness in adults.29,31,32,36,39,41 The largest analysis (n = 4210), the International Childhood Cardiovascular Cohort Consortium (i3C), pooled results from 4 databases (Bogalusa Heart Study, Muscatine Study, Young Finns Study, and the Childhood Determinants of Adult Health study) and used the previous definition of the American Academy of Pediatrics to define childhood abnormal blood pressure and current American Heart Association standards for adult abnormal blood pressure.39 Based on a follow-up of 23 years, the study found that individuals who had persistently elevated blood pressure from childhood to adulthood had a significantly higher risk of carotid intima-media thickness (RR, 1.76 [95% CI, 1.21 to 2.56]).39 Individuals whose abnormal blood pressure normalized during childhood did not have a significantly increased risk (RR, 1.20 [95% CI, 0.86 to 1.67]).
Two studies (age range, 3-18 years) reported significant associations between abnormal childhood and adolescent blood pressure and adult left ventricular hypertrophy.31,40 Based on definitions, the magnitude of associations varied (RRs ranged from 1.30 to 1.59; hazard ratios ranged from 1.92 to 3.41).
Single studies (range of mean age, 10.0-10.9 years) reported significant associations between abnormal childhood and adolescent blood pressure and subclinical cardiovascular disease,31 higher aorta-femoral pulse wave velocity,31 and microalbuminuria, particularly in Black participants.28
Effectiveness of Treatment
Key Question 5. What is the effectiveness of drug, nondrug, and combination interventions for treating high blood pressure in children and adolescents?
Thirteen RCTs with data on more than 2300 participants assessed the efficacy of pharmacological interventions, including angiotensin-converting enzyme inhibitors (Aprilette,48 fosinopril,47 lisinopril49), angiotensin receptor blockers (candesartan,43 losartan,50 olmisartan,51 telmisartan,45 valsartan53), β-blockers(metoprolol succinate extended release [ER]),42 a combination of bisoprolol fumarate and hydrochlorothiazide,46 calcium channel blockers (amlodipine,54 felodipine ER44), and a mineralocorticoid receptor antagonist (eplerenone52). All studies were conducted in mixed populations of children and adolescents. None of the studies provided efficacy outcomes beyond 4 weeks. Telmisartan and a combination of bisoprolol with hydrochlorothiazide are currently not approved by the US Food and Drug Administration for the treatment of children and adolescents.
Most studies excluded children or adolescents with severe hypertension (mostly defined as SBP >20 mm Hg or diastolic blood pressure [DBP] >10 mm Hg above the 99th percentile) or secondary hypertension. The meta-analysis included 12 of the 13 RCTs.59 It combined treatment groups of individual drugs regardless of the dose. Pooled reductions of SBP were –4.38 mm Hg (95% CI, –7.27 to –2.16) for angiotensin-converting enzyme inhibitors, –3.07 mm Hg (95% CI, –4.99 to –1.44) for angiotensin receptor blockers, –3.2 mm Hg (95% CI, –8.69 to –2.23) for β-blockers, –3.1 mm Hg (95% CI, –6.52 to 0.45) for calcium channel blockers, and –0.12 mm Hg (95% CI, –3.69 to 3.46) for mineralocorticoid receptor antagonists.59 The study that was not included in the meta-analysis assessed candesartan in 240 children and adolescents aged 6 to 17 years over 4 weeks.43 Compared with placebo, candesartan led to significantly greater reductions in SBP (–6.56 mm Hg [95% CI not reported]; P < .001) and DBP (–4.76 mm Hg [95% CI not reported]; P = .003).
Pharmacological Treatments Combined With Lifestyle Interventions
In a 6-month, open-label, poor-quality trial (conducted from 1979 to 1981 in the US), a combination of low-dose propranolol/chlorthalidone and an educational program directed toward dietary and exercise modifications for children and parents significantly decreased SBP (–7.6 mm Hg ; P < .001) and DBP(–6.9 mm Hg ; P < .01).55,65 However, propranolol, like other β-blockers, is no longer recommended as a first-line therapy because of the adverse events profile and the lack of association in adults with improved health outcomes.1
Significant decreases in SBP and DBP were achieved by 3 extra weekly school lessons of physical education in hypertensive children (n = 69) aged 9 to 11 years over 8 months (SBP, –4.9 mm Hg [P < .05]; DBP, –3.8 mm Hg [P < .05]);14 by combined resistance and aerobic exercise over 12 weeks for obese, adolescent girls (n = 40; SBP, –8.3 mm Hg [P < .05]; DBP, data not reported);16 and by a DASH (Dietary Approaches to Stop Hypertension)–type diet for overweight adolescents (n = 57) over 3 months (SBP, –2.2 mm Hg [P < .01]; DBP, –2.8 mm Hg [P < .05]).56
Effectiveness of Treatments During Childhood to Reduce Blood Pressure in Adulthood
Key Question 6. What is the effectiveness of drug, nondrug, and combination interventions initiated for the treatment of high blood pressure in children and adolescents for reducing blood pressure and improving other intermediate outcomes in adults?
No studies were identified.
Effectiveness of Treatments During Childhood to Reduce Adverse Health Outcomes in Adulthood
Key Question 7. What is the effectiveness of drug, nondrug, and combination interventions initiated for the treatment of high blood pressure in children and adolescents for reducing adverse health outcomes related to high blood pressure in adults?
No studies were identified.
Harms of Treatment
Key Question 8. What are the adverse effects of drug, nondrug, and combination interventions for treating high blood pressure in children and adolescents?
The included RCTs assessed the risk of harms of ER metoprolol succinate,42 candesartan,43 felodipine ER,44 fosinopril,47 telmisartan,45 and a combination of bisoprolol fumarate and hydrochlorothiazide46 based on data for 909 participants. Overall, risks of experiencing any adverse event and risks of specific adverse events were similar between active treatments and placebo over 2 to 4 weeks.
Pharmacological Treatments Combined With Lifestyle Interventions
No differences in adverse events were reported in the trial with a 6-month follow-up of low-dose propranolol/chlorthalidone in combination with an educational program (see KQ5).55
No data were reported.
This evidence report reviewed studies on the diagnostic accuracy of screening tests for abnormal blood pressure in children and adolescents, studies on the association between childhood and adulthood blood pressure, and studies evaluating the benefits and harms of treatments for abnormal blood pressure in children and adolescents. Table 3 summarizes the evidence by KQ and provides an assessment of the strength of evidence. Compared with the 2013 review for the USPSTF on this topic, 13 RCTs and 1 meta-analysis were added and 4 RCTs were excluded.
No studies evaluated the benefits or harms of screening and the effect of treating childhood hypertension on intermediate and health outcomes in adulthood. The strength of evidence was assessed as low for the single study that reported on the test accuracy of office-based blood pressure measurements. Results of this study might have limited applicability to a screening population because the study population also included children with known hypertension. Overall, the prevalence of hypertension in this population was 29%.
The strength of evidence was low for an association between childhood hypertension and abnormal blood pressure or other intermediate outcomes in adulthood. Studies were very heterogeneous regarding definitions of childhood and adulthood hypertension, the underlying prevalence of hypertension, and outcome measures. Nevertheless, findings consistently demonstrated an association between abnormal childhood and abnormal adulthood blood pressure.
Evidence of moderate strength indicated efficacy and good tolerability of pharmacological interventions, but these studies were mostly limited to participants with primary hypertension. Moreover, none of the drugs were evaluated in more than 1 study. The magnitude of the antihypertensive effects varied across agents and was not always significantly different from that of placebo. The mean age of children in these studies ranged from aged 12 to 14 years; the generalizability of results to younger children or children with secondary hypertension is unknown. For physical exercise and a DASH-type diet, the strength of evidence was low for reducing blood pressure. The evidence was rated as moderate and low for no effect of low-sodium diet and progressive muscle relaxation, respectively.
The main limitation of the methodological approach in this review is that it was limited to literature searches for English-language studies. This strategy might have missed studies conducted in Hispanic children, who have a higher risk for obesity and primary hypertension than non-Hispanic White children.
This review also has several limitations regarding its evidence base. First, no available evidence that directly evaluated the health benefits and harms of screening (KQ1 and KQ3) was identified. Likewise, no evidence on the effect of treating childhood hypertension on intermediate and health outcomes in adulthood could be detected (KQ6 and KQ7). Second, for diagnostic test accuracy of blood pressure measurements (KQ2), there was only 1 study with limited applicability. In addition, thresholds and classifications of hypertension in children are based on normative values and not on health outcomes, like in adults. It is still unclear whether such distribution-based thresholds can adequately distinguish between children with and without hypertension. Furthermore, the exact diagnostic workup in children who screen positive is not well established. Although ABPM is recommended to confirm office-based measurements, normative values and thresholds for hypertension for ABPM are not well founded in children and adolescents. Third, pharmacological treatment studies were small and of very short duration (2 to 4 weeks). No conclusions about the beneficial and harmful effects of long-term pharmacological treatments can be drawn. The mean age of children in these studies ranged from aged 12 to 14 years; the generalizability of results to younger children or children with secondary hypertension is unknown. Fourth, many of the trials included children and adolescents and did not analyze the results separately for these 2 groups. Fifth, although target organ damage because of elevated blood pressure in children is quite common, a causal association with cardiovascular events later in life is difficult to establish.66,67 The ongoing i3C Outcomes study might be able to provide more solid and more direct evidence regarding the association between childhood hypertension and adult cardiovascular events.68
Observational studies indicate an association between hypertension in childhood and hypertension in adulthood. However, the evidence is inconclusive whether the diagnostic accuracy of blood pressure measurements is adequate for screening asymptomatic children and adolescents in primary care.
Source: This article was first published online in the Journal of the American Medical Association on November 10, 2020 (JAMA. 2020;324(18):1884-1895. doi:10.1001/jama.2020.11).
Conflict of Interest Disclosures: None reported.
Funding/Support: This research was funded under contract HHSA-290-2015-00011-I, Task Order 11, from the Agency for Healthcare Research and Quality (AHRQ) under a contract to support the US Preventive Services Task Force (USPSTF).
Role of the Funder/Sponsor: Investigators worked with USPSTF members and AHRQ staff to develop the scope, analytic framework, and key questions for this review. AHRQ had no role in study selection, quality assessment, or synthesis. AHRQ staff provided project oversight, reviewed the report to ensure that the analysis met methodological standards, and distributed the draft for peer review. Otherwise, AHRQ had no role in the conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript findings. The opinions expressed in this document are those of the authors and do not reflect the official position of AHRQ or the US Department of Health and Human Services.
Additional Information: A draft version of the full evidence report underwent external peer review from 3 content experts (Callie Brown, MD, Wake Forest University; Joseph Flynn, MD, University of Washington and Seattle Children’s Hospital; Alex Kemper, MD, MPH, MS, Nationwide Children’s Hospital) and 3 additional federal partner reviewers (National Heart, Lung, and Blood Institute; National Institute on Minority Health and Health Disparities; National Institute of Nursing Research). Comments from reviewers were presented to the USPSTF during its deliberation of the evidence and were considered in preparing the final evidence review.
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31. Xi B, Zhang T, Li S, et al. Can pediatric hypertension criteria be simplified? a prediction analysis of subclinical cardiovascular outcomes from the Bogalusa Heart Study. Hypertension. 2017;69(4):691-696. doi:10.1161/HYPERTENSIONAHA.116.08782
32. Raitakari OT, Juonala M, Kähönen M, et al. Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study. JAMA. 2003;290(17):2277-2283. doi:10.1001/jama.290.17.2277
33. Juhola J, Magnussen CG, Viikari JSA, et al. Tracking of serum lipid levels, blood pressure, and body mass index from childhood to adulthood: the Cardiovascular Risk in Young Finns Study. J Pediatr. 2011;159(4):584-590. doi:10.1016/j.jpeds.2011.03.021
34. Juonala M, Viikari JSA, Hutri-Kähönen N, et al. The 21-year follow-up of the Cardiovascular Risk in Young Finns Study: risk factor levels, secular trends and east-west difference. J Intern Med. 2004;255(4):457-468. doi:10.1111/j.1365-2796.2004.01308.x
35. Juhola J, Oikonen M, Magnussen CG, et al. Childhood physical, environmental, and genetic predictors of adult hypertension: the Cardiovascular Risk in Young Finns Study. Circulation. 2012;126(4):402-409. doi:10.1161/CIRCULATIONAHA.111.085977
36. Oikonen M, Nuotio J, Magnussen CG, et al. Repeated blood pressure measurements in childhood in prediction of hypertension in adulthood. Hypertension. 2016;67(1):41-47. doi:10.1161/HYPERTENSIONAHA.115.06395
37. Aatola H, Koivistoinen T, Tuominen H, et al. Influence of child and adult elevated blood pressure on adult arterial stiffness: the Cardiovascular Risk in Young Finns Study. Hypertension. 2017;70(3):531-536. doi:10.1161/HYPERTENSIONAHA.117.09444
38. Theodore RF, Broadbent J, Nagin D, et al. Childhood to early-midlife systolic blood pressure trajectories: early-life predictors, effect modifiers, and adult cardiovascular outcomes. Hypertension. 2015;66(6):1108-1115. doi:10.1161/HYPERTENSIONAHA.115.05831
39. Juhola J, Magnussen CG, Berenson GS, et al. Combined effects of child and adult elevated blood pressure on subclinical atherosclerosis: the International Childhood Cardiovascular Cohort Consortium. Circulation. 2013;128(3):217-224. doi:10.1161/CIRCULATIONAHA.113.001614
40. Du T, Fernandez C, Barshop R, Chen W, Urbina EM, Bazzano LA. 2017 pediatric hypertension guidelines improve prediction of adult cardiovascular outcomes. Hypertension. 2019;73(6):1217-1223. doi:10.1161/HYPERTENSIONAHA.118.12469
41. Koskinen J, Juonala M, Dwyer T, et al. Utility of different blood pressure measurement components in childhood to predict adult carotid intima-media thickness. Hypertension. 2019;73(2): 335-341. doi:10.1161/HYPERTENSIONAHA.118.12225
42. Batisky DL, Sorof JM, Sugg J, et al; Toprol-XL Pediatric Hypertension Investigators. Efficacy and safety of extended release metoprolol succinate in hypertensive children 6 to 16 years of age: a clinical trial experience. J Pediatr. 2007;150(2):134-139. doi:10.1016/j.jpeds.2006.09.034
43. Trachtman H, Hainer JW, Sugg J, Teng R, Sorof JM, Radcliffe J; Candesartan in Children With Hypertension (CINCH) Investigators. Efficacy, safety, and pharmacokinetics of candesartan cilexetil in hypertensive children aged 6 to 17 years. J Clin Hypertens (Greenwich). 2008;10(10):743-750. doi:10.1111/j.1751-7176.2008.00022.x
44. Trachtman H, Frank R, Mahan JD, et al. Clinical trial of extended-release felodipine in pediatric essential hypertension. Pediatr Nephrol. 2003;18(6):548-553. doi:10.1007/s00467-003-1134-0
45. Wells TG, Portman R, Norman P, Haertter S, Davidai G, FeiWang. Safety, efficacy, and pharmacokinetics of telmisartan in pediatric patients with hypertension. Clin Pediatr (Phila). 2010;49(10):938-946. doi:10.1177/0009922810363609
46. Sorof JM, Cargo P, Graepel J, et al. β-blocker/thiazide combination for treatment of hypertensive children: a randomized double-blind, placebo-controlled trial. Pediatr Nephrol. 2002;17(5):345-350. doi:10.1007/s00467-002-0851-0
47. Li JS, Berezny K, Kilaru R, et al. Is the extrapolated adult dose of fosinopril safe and effective in treating hypertensive children? Hypertension. 2004;44(3):289-293. doi:10.1161/01. HYP.0000138069.68413.f0
48. Wells T, Frame V, Soffer B, et al; Enalapril Pediatric Hypertension Collaborative Study Group. A double-blind, placebo-controlled, dose-response study of the effectiveness and safety of enalapril for children with hypertension. J Clin Pharmacol. 2002;42(8):870-880. doi:10.1177/009127002401102786
49. Soffer B, Zhang Z, Miller K, Vogt BA, Shahinfar S. A double-blind, placebo-controlled, dose-response study of the effectiveness and safety of lisinopril for children with hypertension. Am J Hypertens. 2003;16(10):795-800. doi:10.1016/S0895-7061(03)00900-2
50. Shahinfar S, Cano F, Soffer BA, et al. A double-blind, dose-response study of losartan in hypertensive children. Am J Hypertens. 2005;18(2, pt 1):183-190. doi:10.1016/j.amjhyper.2004.09.009
51. Hazan L, Hernández Rodriguez OA, Bhorat AE, Miyazaki K, Tao B, Heyrman R; Assessment of Efficacy and Safety of Olmesartan in Pediatric Hypertension Study Group. A double-blind, dose-response study of the efficacy and safety of olmesartan medoxomil in children and adolescents with hypertension. Hypertension. 2010;55(6):1323- 1330. doi:10.1161/HYPERTENSIONAHA.109.147702
52. Li JS, Flynn JT, Portman R, et al. The efficacy and safety of the novel aldosterone antagonist eplerenone in children with hypertension: a randomized, double-blind, dose-response study. J Pediatr. 2010;157(2):282-287. doi:10.1016/j.jpeds.2010.02.042
53. Wells T, Blumer J, Meyers KEC, et al; Valsartan Pediatric Hypertension Study Group. Effectiveness and safety of valsartan in children aged 6 to 16 years with hypertension. J Clin Hypertens (Greenwich). 2011;13(5):357-365. doi:10.1111/j.1751-7176.2011.00432.x
54. Flynn JT, Newburger JW, Daniels SR, et al; PATH-1 Investigators. A randomized, placebo-controlled trial of amlodipine in children with hypertension. J Pediatr. 2004;145(3):353-359. doi:10.1016/j.jpeds.2004.04.009
55. Berenson GS, Voors AW, Webber LS, et al. A model of intervention for prevention of early essential hypertension in the 1980s. Hypertension. 1983;5(1):41-54. doi:10.1161/01.HYP.5.1.41
56. Couch SC, Saelens BE, Levin L, Dart K, Falciglia G, Daniels SR. The efficacy of a clinic-based behavioral nutrition intervention emphasizing a DASH-type diet for adolescents with elevated blood pressure. J Pediatr. 2008;152(4):494-501. doi:10.1016/j.jpeds.2007.09.022
57. Howe PRC, Cobiac L, Smith RM. Lack of effect of short-term changes in sodium intake on blood pressure in adolescent schoolchildren. J Hypertens. 1991;9(2):181-186. doi:10.1097/00004872-199102000-00014
58. Sinaiko AR, Gomez-Marin O, Prineas RJ. Effect of low sodium diet or potassium supplementation on adolescent blood pressure. Hypertension. 1993;21(6, pt 2):989-994. doi:10.1161/01.hyp.21.6.989
59. Burrello J, Erhardt EM, Saint-Hilary G, et al. Pharmacological treatment of arterial hypertension in children and adolescents: a network meta-analysis. Hypertension. 2018;72(2):306-313. doi:10.1161/HYPERTENSIONAHA.118.10862
60. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. 2004;114(2 suppl 4th report):555-576.
61. Dwyer T, Magnussen CG, Schmidt MD, et al. Decline in physical fitness from childhood to adulthood associated with increased obesity and insulin resistance in adults. Diabetes Care. 2009;32(4):683-687. doi:10.2337/dc08-1638
62. Ceponiene I, Klumbiene J, Tamuleviciute- Prasciene E, et al. Associations between risk factors in childhood (12-13 years) and adulthood (48-49 years) and subclinical atherosclerosis: the Kaunas Cardiovascular Risk Cohort Study. BMC Cardiovasc Disord. 2015;15(1):89. doi:10.1186/s12872-015-0087-0
63. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018;138(17):e426-e483. doi:10.1161/cir.0000000000000597
64. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520. doi:10.1001/jama.2013.284427
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67. Brady TM, Fivush B, Flynn JT, Parekh R. Ability of blood pressure to predict left ventricular hypertrophy in children with primary hypertension. J Pediatr. 2008;152(1):73-78. doi:10.1016/j.jpeds.2007.05.053
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Evidence reviews for the US Preventive Services Task Force (USPSTF) use an analytic framework to visually display key questions addressed by the review to allowthe USPSTF to evaluate the effectiveness and safety of a preventive service. The questions are depicted by linkages that relate interventions to outcomes. A dashed line indicates a health outcome that precedes subsequent outcomes. Refer to the USPSTF procedure manual for further details.10
a Includes left ventricular hypertrophy, urinary albumin excretion (microalbuminuria), intima-media thickness (measured at carotid arteries, femoral arteries, or both), and retinal vascular changes.
|Age, y||Elevated blood pressure||Hypertension|
|Stage 1||Stage 2|
|1-13||The lower of:
Systolic 120-129 mm Hg
Diastolic <80 mm Hg
|The lower of:
≥95th percentile to <95th percentile + 12 mm Hg
Systolic 130-139 mm Hg
Diastolic 80-89 mm Hg
|The lower of:
≥95th percentile + 12 mm Hg
Systolic ≥140 mm Hg systolic
Diastolic ≥90 mm Hg
|≥13||Systolic 120-129 mm Hg
Diastolic <80 mm Hg
|Systolic 130-139 mm Hg
Diastolic 80-89 mm Hg
|Systolic ≥140 mm Hg
Diastolic ≥90 mm Hg
|Standard||Adult hypertension standards||Nonstandard adult hypertension|
|Current childhood hypertension standards1||1 publication40 (n = 3940)
RRs range from 1.45 to 1.66 (all statistically significant)
|1 publication40 (n = 3940)
RRs range from 1.62 to 1.98 (all statistically significant)
|Prior childhood hypertension standards60||2 publications37,39,40 (n >5480)
RRs range from 1.49 to 1.65 (all statistically significant)
RRs range from 1.53 to 1.95 (all statistically significant)
HRs range from 2.8 to 3.2 (all statistically significant)
AUC range, 0.60-0.63
|1 publication35 (n = 2625)
OR, 2.12 (95% CI, 1.82 to 2.61)
|Nonstandard childhood hypertension definitions||0 publications||0 publications||7 publications17,18,24-27,30 (n = 4790)
ORs and RRs range from 1.1 to 9.0, generally excluding the null
Abbreviations: AUC, area under the receiver operating characteristic curve; HR, hazard ratio; OR, odds ratio; PPV, positive predictive value; RR, relative risk.
a Abnormal blood pressure defined as SBP greater than 120 mm Hg and DPB greater than 80 mm Hg or self-reporting of antihypertensive medication use.63
b Hypertension defined as SBP 140 mm Hg or greater or DBP 90 mm Hg or greater or self-reported antihypertensive medication use.64
|No. of studies
(No. of participants)
|Summary of findings||Consistency/precision||Other limitations||EPC assessment of strength of evidence||Applicability|
|KQ1: Direct benefits of screening|
|No studies identified||NA||NA||NA||NA||NA|
|KQ2: Diagnostic test accuracy|
|Sensitivity and specificity||1 cross-sectional study23 (247)||Sensitivity of office-based BP measurements, 81.6%
|Consistency unknown (single study body of evidence)/imprecise||Body of evidence limitations: moderate
Reporting bias: not detected
|Low for diagnostic test accuracy measures||Limited applicability; only 2 office-based measurements: population included children with known abnormal blood pressure|
|KQ3: Harms of screening—No studies identified|
|No studies identified||NA||NA||NA||NA||NA|
|KQ4: Association between high BP in children and high BP or intermediate outcomes in adults|
|Association between BP in children and adults||20 longitudinal cohort studies17,18,24-39 (>9687)a||Low to moderate sensitivity and PPV for relationship between childhood and adult abnormal BP; results consistent despite variable definitions||Consistent/imprecise||Body of evidence limitations: high
Reporting bias: NA
|Low for association between abnormal BP in childhood and abnormal BP in adulthood||Applicability varies because prevalence of hypertension is widely variable|
|Association between BP in children and intermediate outcomes in adults||7 longitudinal cohort studies28,29,31,32,36,40,41 (>5925)a||
OR for CIMT, 1.24; HRs range from 2.03 to 3.07
Weak correlations between abnormal BP in childhood and CIMT in adulthood (ranging from 0.04 to 0.16)
|Consistent/imprecise||Body of evidence limitations: high
Reporting bias: NA
|Low for CIMT||Applicability varies because prevalence of hypertension is widely variable|
|Key question 5: Effectiveness of interventions|
|13 RCTs42-54 (2476)||Reductions of SBP for:
ACE inhibitors: −4.38 mm Hg
ARBs: −3.07 mm Hg
β-Blockers: −3.20 mm Hg
Calcium channel blockers: 3.10 mm Hg
Mineralocorticoid receptor antagonists: −0.12 mm Hg
All comparisons with placebo after 2 to 4 wk
|Consistent/imprecise||Body-of-evidence limitations: moderate
Reporting bias: not detected
|Moderate for benefit||Applies to children and adolescents aged 6 to 18 y with BP above the 95th percentile; severe hypertension and secondary hypertension were excluded from most studies; study durations up to 4 wk; no long-term studies|
|Pharmacological + lifestyle intervention||1 RCT55,65 (141)||Statistically significant reductions of SBP (−7.6 mm Hg) and DBP (−6.9 mm Hg) compared with control after 6 mo||Consistency unknown (single study body of evidence)/precise||Body-of-evidence limitations: high
Reporting bias: not detected
|Low for benefit||Applies to children and adolescents aged 8 to 18 y with BP above the 90th percentile|
|Low-sodium diet||2 RCTs57,58 (313)||No clinically relevant differences in DBP or SBP compared with control||Consistent/imprecise||Body-of-evidence limitations: moderate
Reporting bias: not detected
|Moderate for no benefit||Applies to children and adolescents age 11 to 18 y with BP above the 85th percentile|
|DASH diet||1 RCT56 (57)||Statistically significant reduction of SBP (−2.2 mm Mg; P < .01) and DBP (−2.8 mm Hg; P < .05) at the end of intervention (3 mo) compared with control
At 6-mo follow-up, similar BP measurements between treatment and control groups (SBP, 120.1 vs 120.0 mm Hg; DBP, 75.2 vs vs 76.4 mm Hg)
|Consistency unknown (single study body of evidence)/imprecise||Body-of-evidence limitations: moderate
Reporting bias: not detected
|Low for benefit||Applies to children and adolescents age 11 to 18 y with BP above the 90th percentile|
|Physical exercise||2 RCTs14,16 (109)||Statistically significant reductions in SBP (−4.9 mm Hg; P < .05) and DBP (−3.8 mm Hg; P < .05) in children aged 9 to 11 years after 8 mo
Statistically significant reduction in SBP (−8.3 mm Hg; P < .05) but not DBP (data not reported) in obese adolescent girls after 3 mo
|Consistent/imprecise||Body-of-evidence limitations: moderate
Reporting bias: not detected
|Low for benefit||Applies to children age 9 to 11 y with BP above the 95th percentile and obese adolescent girls with elevated BP|
|Progressive muscle relaxation||1 RCT15 (159)||No clinically relevant differences in SBP or DBP compared with control||Consistency unknown (single study body of evidence)/imprecise||Body-of-evidence limitations: moderate
Reporting bias: not detected
|Low for no benefit||Applies to children and adolescents age 13 to 17 y with BP above the 85th percentile|
|KQ6: Effectiveness of interventions on intermediate outcomes in adulthood—No studies identified|
|KQ7: Effectiveness of interventions on health outcomes in adult|
|KQ8: Harms of interventions|
|Pharmacological interventions||6 RCTs42-45,47 (909)||Similar risks of overall adverse events between pharmacological treatments (β-blocker, calcium channel blockers, ACE inhibitors, or ARBs) and placebo over 2 to 4 wk||Consistent/very imprecise||Body-of-evidence limitations: moderate||Low for similar harms||Applies to children and adolescents age 6 to 18 y with BP above the 95th percentile; severe hypertension and secondary hypertension were excluded; study durations up to 4 wk; no long-term studies|
|Pharmacological treatments combined with lifestyle interventions||1 RCT55 (150)||Similar risks of overall adverse events between pharmacological treatment (propranolol + chlorothalidone) plus lifestyle interventions and no intervention||NA/very imprecise||Body-of-evidence limitations: moderate
Indirectness: propranolol not recommended anymore as first line treatment
|Very low for similar harms||Applies to children and adolescents aged 6 to 18 y with BP above the 90th percentile|
Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BP, blood pressure; CIMT, carotid intima-media thickness; DASH, Dietary Approaches to Stop Hypertension; DBP, diastolic blood pressure; HR, hazard ratio; KQ, key question; NA, not applicable; PPV, positive predictive value; RCT, randomized clinical trial; SBP, systolic blood pressure.
a Studies drew from overlapping cohorts and may include the same participants.